Penicillins

The first to be discovered and most widely used of all the antibiotics. Sir Alexander Fleming first noted the action of the penicillium mould on Staphylococcus aureus in 1928. However it wasn't until 1940 that Florey¹ and Chain isolated the active substance, and produced a life-saving antibiotic that changed the prognosis for many of the casualties of the Second World War.

This class of antibiotics are particularly safe because they act on bacterial cell walls, a structure not found in mammals.

• Cell walls are composed of peptidoglycan and to form it sugars and peptides need to be linked together by an enzyme called transpeptidase.
• Penicillin blocks the action of this enzyme so that when bacteria divide to make new cells, the walls do not form correctly. They break and the bacterial cell is killed.
• However, most S. aureus now produce penicillinase, so further modification of the basic penicillin structure has produced antibiotics that can withstand penicillinase, and remain effective, e.g. methicillin.
• They penetrate well into body tissues and fluids, except for the cerebrospinal fluid. This is improved if the meninges are inflamed.
• They are excreted in high concentrations in the urine.

• Penicillin G (benzylpenicillin), penicillin V (phenoxymethylpenicillin)
• Penicillinase resistant penicillin: flucloxacillin
• Broad spectrum penicillins: amoxicillin, ampicillin, co-amoxiclav
• Anti-pseudomonal penicillins: piperacillin, ticarcillin

They are available topically, orally or intravenously. They should not be given intrathecally as they may cause encephalopathy which can be fatal.

Where possible treatment should be guided by sensitivities from a cultured specimen.Where empiric treatment is necessary the local primary care trust will produce a formulary, based on knowledge of local prevalent pathogens and resistance.

• Hypersensitivity to penicillin, which is considered in detail below.
• Combined oral contraceptives; patients should be advised to use extra precautions for the treatment course plus seven days.

• The most important of these is HYPERSENSITIVITY. Penicillin is one of the most frequently cited allergies amongst patients, but the history may be vague. Even with a convincing history, a high proportion, up to 28%² may still prove to be penicillin tolerant after skin testing.
  • Anaphylactic reactions, which may be fatal, occur in less than 0.05% of treated patients.³
  • Other forms of allergy, e.g. rash, urticaria occur in approximately 1-10% of exposed patients.
  • Patients with other atopy e.g. asthma or hay fever, are more likely to be allergic to penicillin.
  • Patients who develop a rash immediately after taking penicillin, should not receive further doses.
  • They should also NOT have a different form of penicillin, cephalosporin or other beta-lactam antibiotic.The cross-reactivity with cephalosporins varies according to which type is prescribed. Cross reactivity between penicillins and second and third generation cephalosporins is low and may be lower than the cross reactivity between penicillins and unrelated antibiotics.⁴ It may be as low as 4-5% with a 3rd generation/ no benzyl ring cephalosporin.⁵
  • If the rash develops 72 hours or more after taking the penicillin, it is almost certainly not penicillin anaphylaxis. However it may still be a reaction to the penicillin and a risk-benefit analysis should assess the benefit to the patient of switching to an alternative treatment.
  • Life-saving treatment should NOT be withheld.
  • In life threatening infections such as bacterial meningitis, septicaemia, and severe respiratory tract infections, a second or third generation cephalosporin should be considered even in patients with a history of penicillin allergy.⁴
• Encephalopathy due to cerebral irritation, is a rare but serious effect. This can occur in patients with severe renal failure, or in patients who are given very high doses.
• In patients with renal failure there may be an accumulation of sodium or potassium, which is a constituent of intravenous penicillins.
• Diarrhoea occurs frequently with broad spectrum, oral penicillins.
• If antibiotic associated pseudo-membranous colitis is suspected, maintain patient's hydration, withhold/substitute suspected antibiotic and send stool sample for Clostridium difficile toxin detection. If confirmed and symptomatic start metronidazole as first line treatment. Vancomycin or other drugs can be used if that fails.